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Am J Neurodegener Dis 2013;2(4):266-275

Original Article
Diversity of pathological features other than Lewy bodies in familial
Parkinson’s disease due to SNCA mutations

Hiroshige Fujishiro, Akiko Yamashita Imamura, Wen-Lang Lin, Hirotake Uchikado, Margery H Mark, Lawrence I Golbe,
Katerina Markopoulou, Zbigniew K Wszolek, Dennis W Dickson

Departments of Neuroscience, Neurology, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Robert Wood
Johnson Medical School, New Brunswick, NJ; Department of Neurology, University of Thessaly, Greece; Current
address: Hiroshige Fujishiro, Juntendo University School of Medicine, Tokyo, Japan. Equal contributors.

Received October 24, 2013; Accepted November 18, 2013; Epub November 29, 2013; Published December 15, 2013

Abstract: The clinical features of the genetically determined forms of familial Parkinson’s disease (PD) have been
described in multiple reports, but there have been few comparative neuropathologic studies. Five familial PD cases,
with mutations in SNCA, were matched for age, sex, and Alzheimer type pathology with sporadic PD cases.
Immunohistochemistry for phospho-tau and α-synuclein was performed in 8 brain regions. The frequency of tau
pathology and the morphologic features of α-synuclein pathology in familial PD were compared with sporadic PD using
semi-quantitative methods. In familial PD, there were significantly more tau positive extra-perikaryal spheroid-like and
thread-like lesions than in the sporadic PD. There was no significant difference in the amount of α-synuclein positive
neuronal perikaryal pathology between familial PD and sporadic PD, but α-synuclein positive oligodendroglial and
neuritic lesions were significantly greater in familial PD compared to sporadic PD. In the substantia nigra, familial PD
had more marked neuronal loss and fewer residential neurons with Lewy bodies than the sporadic PD, suggesting a
close relationship between the severity of neuronal loss and Lewy body formation. The results show a diversity of
pathological features of genetically determined familial PD, and they draw attention to the possible role of tau protein in
neurodegeneration. Moreover, the presence of oligodendroglial inclusions at the light and electron microscopic levels
in familial PD suggests that PD and multiple system atrophy form a continuum of α-synuclein pathology.
(AJND1310002).

Keywords: Pathological features, Lewy bodies, familial Parkinson’s disease, SNCA mutations

Address correspondence to: Dr. Dennis W Dickson, Department of Neuroscience, Mayo Clinic, 4500 San Pablo
Road, Jacksonville, FL 32224, USA. Tel: 904-953-7137; Fax: 904-953-7117; E-mail: dickson.dennis@mayo.edu